rs886053407

Variant names:

• chr17-75721600-T-C
• rs886053407
• NM_000213.5:c.-23T>C

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_000213.5(ITGB4):​c.-23T>C variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000302 in 152,072 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.00030 (1 hom., cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: ITGB4 NM_000213.5 5_prime_UTR
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -4.44
• Publications: 0 publications found

Genes affected

ITGB4 (HGNC:6158): (integrin subunit beta 4) Integrins are heterodimers comprised of alpha and beta subunits, that are noncovalently associated transmembrane glycoprotein receptors. Different combinations of alpha and beta polypeptides form complexes that vary in their ligand-binding specificities. Integrins mediate cell-matrix or cell-cell adhesion, and transduced signals that regulate gene expression and cell growth. This gene encodes the integrin beta 4 subunit, a receptor for the laminins. This subunit tends to associate with alpha 6 subunit and is likely to play a pivotal role in the biology of invasive carcinoma. Mutations in this gene are associated with epidermolysis bullosa with pyloric atresia. Multiple alternatively spliced transcript variants encoding distinct isoforms have been found for this gene. [provided by RefSeq, Jul 2008]

ITGB4 Gene-Disease associations (from GenCC):

• epidermolysis bullosa simplex

  Inheritance: AD Classification: DEFINITIVE Submitted by: G2P
• junctional epidermolysis bullosa with pyloric atresia

  Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Ambry Genetics, Genomics England PanelApp, G2P, Orphanet
• junctional epidermolysis bullosa, non-Herlitz type

  Inheritance: AR Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae), Genomics England PanelApp
• aplasia cutis congenita

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• epidermolysis bullosa simplex 5C, with pyloric atresia

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
• generalized junctional epidermolysis bullosa non-Herlitz type

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
• localized junctional epidermolysis bullosa, non-Herlitz type

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
• epidermolysis bullosa simplex 1C, localized

  Inheritance: Unknown Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.78).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000213.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ITGB4	NM_000213.5	MANE Select	c.-23T>C		5_prime_UTR	Exon 1 of 40	NP_000204.3
	ITGB4	NM_001005619.2		c.-23T>C		5_prime_UTR	Exon 1 of 40	NP_001005619.1
	ITGB4	NM_001005731.3		c.-23T>C		5_prime_UTR	Exon 1 of 39	NP_001005731.1	P16144-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ITGB4	ENST00000200181.8	TSL:1 MANE Select	c.-23T>C		5_prime_UTR	Exon 1 of 40	ENSP00000200181.3	P16144-1
	ITGB4	ENST00000449880.7	TSL:1	c.-23T>C		5_prime_UTR	Exon 1 of 40	ENSP00000400217.2	P16144-3
	ITGB4	ENST00000450894.7	TSL:1	c.-23T>C		5_prime_UTR	Exon 1 of 39	ENSP00000405536.3	P16144-2

Frequencies

GnomAD3 genomes AF: 0.000302 AC: 46 AN: 152072 Hom.: 1 Cov.: 32

Gnomad AFR AF: 0.0000241

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.000189

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000618

Gnomad OTH AF: 0.000479

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 302 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 234

African (AFR) AF: 0.00 AC: 0 AN: 2

American (AMR) AF: 0.00 AC: 0 AN: 2

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2

East Asian (EAS) AF: 0.00 AC: 0 AN: 6

South Asian (SAS) AF: 0.00 AC: 0 AN: 4

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 274

Other (OTH) AF: 0.00 AC: 0 AN: 12

GnomAD4 genome AF: 0.000302 AC: 46 AN: 152072 Hom.: 1 Cov.: 32 AF XY: 0.000310 AC XY: 23 AN XY: 74300

African (AFR) AF: 0.0000241 AC: 1 AN: 41410

American (AMR) AF: 0.00 AC: 0 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5166

South Asian (SAS) AF: 0.00 AC: 0 AN: 4830

European-Finnish (FIN) AF: 0.000189 AC: 2 AN: 10610

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.000618 AC: 42 AN: 67990

Other (OTH) AF: 0.000479 AC: 1 AN: 2086

Alfa AF: 0.000918 Hom.: 0

Bravo AF: 0.000155

ClinVar

ClinVar submissions as Germline

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	Junctional epidermolysis bullosa with pyloric atresia (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	1.1
DANN	Benign	0.60
PhyloP100		-4.4
PromoterAI		0.13	Neutral

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs886053407; hg19: chr17-73717680;